This project was originally designed to (1) evaluate the angiogenic and cellular proliferative properties of epidermal growth factor (EGF) and fibroblast growth factor (FGF) placed in high concentration in various parts of the eye and (2) to determine aging changes in Bruch's membrane that, in the presence of angiogenic factors, could predispose to subretinal neovascularization. In the previous two years of the project, a technique of incorporating the growth substances in Elvax for slow release into adjacent tissue was developed. Inflammatory response from antigen-antibody reaction was shown to cause neovascularization. EGF and prostaglandins caused neovascularization mediated through inflammatory cells. FGF caused neovascularization without inflammatory cells, presumably by direct action on vascular endothelium, both in the cornea and on the iris. Scanning electron microscopy revealed surface features of pigment epithelium and layers of Bruch's membrane not previously seen. In the next year neovascularization will be attempted under the retina and into the vitreous cavity by implanting Elvax pellets with growth factors under the retina and in the vitreous cavity. Angiogenic and cellular proliferation effects of growth factors will be evaluated after injury to the internal limiting lamina of the retina, and to Bruch's membrane. Platelet growth factor will be evaluated. Pathology and aging of Bruch's membrane will be examined by scanning electron microscopy. The significance of the work is to try to produce and understand retinovitreal neovascularization, as in diabetes, and subretinal neovascularization, both of which are the leading cause of blindness.